RESUMO
Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long-Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues' influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fos-immunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment's potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context-driven ethanol seeking.
Assuntos
Comportamento de Procura de Droga , Etanol , Extinção Psicológica , Núcleo Accumbens , Ratos Long-Evans , Animais , Núcleo Accumbens/efeitos dos fármacos , Masculino , Etanol/administração & dosagem , Etanol/farmacologia , Comportamento de Procura de Droga/fisiologia , Ratos , Extinção Psicológica/fisiologia , Extinção Psicológica/efeitos dos fármacos , Autoadministração , Vias Neurais/fisiologia , Alcoolismo , Sinais (Psicologia) , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Baclofeno/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Muscimol/farmacologiaRESUMO
Ethanol is the most consumed substance of abuse in the world, and its misuse may lead to the development of alcohol use disorder (AUD). High relapse rates remain a relevant problem in the treatment of AUD. Exposure to environmental cues previously associated with ethanol intake could trigger ethanol-seeking behavior. However, the neural mechanisms involved in this phenomenon are not entirely clear. In this context, cortical projections to the basolateral amygdala (BLA) play a role in appetitive and aversive learned behaviors. Therefore, we aimed to evaluate the activation of the cortical projections from the prelimbic (PL), orbitofrontal (OFC), and infralimbic (IL), to the BLA in the context-induced reinstatement of ethanol-seeking. Male Long-Evans rats were trained to self-administer 10% ethanol in Context A. Subsequently, lever pressing in the presence of the discrete cue was extinguished in Context B. After nine extinction sessions, rats underwent intracranial surgery for the unilateral injection of red fluorescent retrograde tracer into the BLA. The context-induced reinstatement of ethanol-seeking was assessed by re-exposing the rats to Context A or B under extinction conditions. Finally, we combined retrograde neuronal tracing with Fos to identify activated cortical inputs to BLA during the reinstatement of ethanol-seeking behavior. We found that PL, but not OFC or IL, retrogradely-labeled neurons from BLA presented increased Fos expression during the re-exposure to the ethanol-associated context, suggesting that PL projection to BLA is involved in the context-induced reinstatement of ethanol-seeking behavior.
Assuntos
Alcoolismo , Complexo Nuclear Basolateral da Amígdala , Ratos , Masculino , Animais , Etanol/farmacologia , Extinção Psicológica , Ratos Sprague-Dawley , Tonsila do Cerebelo/fisiologia , Ratos Long-Evans , Sinais (Psicologia) , AutoadministraçãoRESUMO
Parkinson's disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine-inhibitor of VMAT2-has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.
RESUMO
BACKGROUND: Ethanol use is related to a wide variety of negative health outcomes, including cardiovascular diseases. Stress is also involved in numerous pathologies, such as cardiovascular diseases and psychiatric disorders. Sexual dimorphism is an important factor affecting cardiovascular response and has been proposed as a potential risk factor for sex-specific health problems in humans. Here, we evaluated the effect of prolonged ethanol vapor inhalation on arterial pressure, heart rate, and tail skin temperature responses to acute restraint stress, investigating differences between male and female rats. METHODS: We exposed male and female Long-Evans rats to ethanol vapor for 14 h, followed by ethanol withdrawal for 10 h, for 30 consecutive days, or to room air (control groups). The animals underwent surgical implantation of a cannula into the femoral artery for assessment of arterial pressure and heart rate values. The tail skin temperature was measured as an indirect measurement of sympathetic vasomotor response. RESULTS: Chronic ethanol vapor inhalation reduced basal heart rate in both female and male rats. Sex-related difference was observed in the decrease of tail cutaneous temperature evoked by stress, but not in the pressor and tachycardiac responses. Furthermore, prolonged ethanol inhalation enhanced the blood pressure and heart rate increase caused by acute restraint stress in male, but not in female rats. However, no effect of chronic ethanol vapor was observed in the tail cutaneous temperature response to restraint in either sex. CONCLUSION: Chronic ethanol vapor exposure increased the cardiovascular reactivity to stress in male, but not in female rats.
Assuntos
Etanol/toxicidade , Caracteres Sexuais , Animais , Doenças Cardiovasculares , Feminino , Masculino , Ratos , Ratos Long-Evans , Estresse Fisiológico , Estresse PsicológicoRESUMO
The endocannabinoid system is implicated in anxiety, but the brain sites involved are not completely understood. The bed nucleus of the stria terminalis (BNST) has been related to anxiety and responses to aversive threats. Besides, endocannabinoid neurotransmission acting via CB1 receptors was identified in the BNST. However, the presence of CB2 receptors and the role of BNST endocannabinoid system in anxiety-like behaviors have never been reported. Therefore, this study investigated the presence of CB1 and CB2 receptors in the BNST and their role in anxiety-like behaviors. For this, gene expression of the endocannabinoid receptors was evaluated in samples from anterior and posterior BNST. Besides, behaviors were evaluated in the elevated plus-maze (EPM) in unstressed rats (trait anxiety-like behavior) and after exposure to restraint stress (restraint-evoked anxiety-like behavior) in rats treated with either the CB1 receptor antagonist AM251 or the CB2 receptor antagonist JTE907 into the anterior BNST. The presence of CB1 and CB2 receptors gene expression was identified in anterior and posterior divisions of the BNST. Bilateral microinjection of AM251 into the anterior BNST dose-dependently increased EPM open arms exploration in unstressed animals and inhibited the anxiety-like behavior in the EPM evoked by restraint. Conversely, intra-BNST microinjection of JTE907 decreased EPM open arms exploration in a dose-dependent manner and inhibited restraint-evoked behavioral changes in the EPM. Taken together, these results indicate that CB1 and CB2 receptors present in the BNST are involved in control of anxiety-like behaviors, and control by the latter is affected by previous stress experience.
Assuntos
Ansiedade/psicologia , Endocanabinoides/metabolismo , Núcleos Septais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais , Antagonistas de Receptores de Canabinoides , Dioxóis/administração & dosagem , Expressão Gênica , Masculino , Modelos Neurológicos , Piperidinas/administração & dosagem , Pirazóis/administração & dosagem , Quinolonas/administração & dosagem , Ratos , Ratos Wistar , Restrição Física/efeitos adversos , Núcleos Septais/metabolismoRESUMO
Editorial crítico-analítico da situação político-social do país, denunciando os movimentos autoritários que o (des)governo bolsonaro vem implementando em plena pandemia de coronavirus, na direção de uma tentantiva de quebra do estado de direito. Trás reflexões sobre a educação e a educação física em tempos de Covid-19, bem como aponta questões sobre temas a serem considerados na realidade pós-pandemia.
RESUMO
BACKGROUND: Alcohol abuse is a health concern worldwide. Studies have associated alcohol abuse with cardiovascular impairments. In this study, we investigated differences in the effects of chronic alcohol vapor exposure on cardiovascular function between male and female rats by using the alcohol vapor chamber method to induce alcohol addiction-like behaviors in rats. METHODS: We exposed male and female Long-Evans rats to alcohol vapor for 14 hours, followed by ethanol withdrawal for 10 hours, for 30 consecutive days or room air (control groups). The animals underwent preparation for the surgical implantation of cannulas into femoral vessels, for allowing the assessment of the basal arterial pressure and heart rate values, baroreflex function, and autonomic activity. RESULTS: Female control rats showed higher basal heart rate compared to male control rats. Chronic alcohol vapor inhalation reduced basal heart rate in females, but not in males; this effect was followed by an increase in the parasympathetic tone of the heart. Further, female rats subjected to alcohol vapor showed an increase in the baroreflex activity. CONCLUSIONS: These findings suggest that females are more sensitive to chronic alcohol vapor exposure than males because they had a reduction in basal heart rate and changes in the baroreflex activity.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Administração por Inalação , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Feminino , Masculino , Ratos Long-EvansRESUMO
A partir do reconhecimento das implicações das tecnologias digitais de informação e comunicação (TDIC) e da mídia no âmbito da educação, esse estudo buscou analisar as propostas curriculares dos cursos de Educação Física - Licenciatura oferecidos por universidades federais brasileiras, identificando possíveis abordagens no uso das mídias e das tecnologias em seus componentes curriculares. Metodologicamente, a pesquisa qualitativa documental-descritiva realizou um levantamento de dados dos projetos pedagógicos de cursos de licenciatura em Educação Física distribuídos nas universidades federais. Para isso, se procedeu a identificação de componentes curriculares que tematizam as TDIC/mídia, a sua natureza quanto à obrigatoriedade ou não, assim como a sua caracterização quanto à abordagem teórico-metodológica. Os resultados mostraram que os cursos de formação de professores de Educação Física das instituições investigadas ainda têm um longo caminho a percorrer no que diz respeito a integração da temática que envolve as TDIC/mídia nos currículos.
From the recognition of the implications of digital information and communication technologies (DICT) in the field of education, this study analyzed how curricular proposals of Physical Education courses graduation, offered by Brazilian Federal Universities, identifying possible approaches about media and digital technologies in its curricular components. Methodologically, the qualitative documental-descriptive research carried out a survey of data of the pedagogical projects of undergraduate courses in Physical Education distributed in the federal universities. To do this, we proceed to identify the curricular components that are referred to as DICT / media; the kind of curricular components with regard to compulsory or not; as well as its characterization in the theoreticalmethodological approach. The results show that the training courses of physical education teachers of the institutions investigated still have a long way to go in regards to the integration of the issue that involves the technologies/media in the curriculum.
Con el reconocimiento de las implicaciones de las tecnologías digitales en el ámbito de la educación, este estudio ha analizado las propuestas curriculares de grados de formación de profesorado de Educación Física ofertados por universidades federales brasileñas, identificando posibles aproximaciones en el uso de los medios y de las tecnologías en sus asignaturas. Para su elaboración, se ha utilizado una metodología cualitativa documental-descriptiva que realizó una recogida de datos de las propuestas de grados de Educación Física distribuidos en las universidades federales. Para ello se procedió a la identificación de las asignaturas que trataban de las TDIC/medios, la naturaleza de las disciplinas en el currículo obligatorias u optativa, y su caracterización en relación a su aproximación teórico-metodológica. Los resultados muestran que los grados de formación de profesorado de las instituciones investigadas cuentan con un largo recorrido hasta la integración de la temática que trata de las TDIC/medios en los currículos.
Assuntos
Educação Física e Treinamento/métodos , Tecnologia Educacional , Capacitação de Professores/métodosRESUMO
Evidence indicates that drug relapse in humans is often provoked by exposure to the self-administered drug-associated context. An animal model called "ABA renewal procedure" has been used to study the context-induced relapse to drug seeking. Here, we reported a new and feasible training procedure for the ABA renewal method to explore the role of the prelimbic cortex in context-induced relapse to ethanol seeking. By using a saccharin fading technique, we trained rats to self-administer ethanol (10%). The drug delivery was paired with a discrete tone-light cue. Lever pressing was subsequently extinguished in a non-drug-associated context in the presence of the discrete cue. Rats were subsequently tested for reinstatement in contexts A or B, under extinction conditions. Ethanol-associated context induced the reinstatement of ethanol seeking and increased the expression of Fos in the prelimbic cortex. The rate of neural activation in the prelimbic cortex was 3.4% in the extinction context B and 7.7% in the drug-associated context A, as evidenced by double-labeling of Fos and the neuron-specific protein NeuN. The reversible inactivation of the neural activity in the prelimbic cortex with gamma-Aminobutyric acid (GABA) receptor agonists (muscimol + baclofen) attenuated the context-induced reinstatement of ethanol self-administration. These results demonstrated that the neuronal activation of the prelimbic cortex is involved in the context-induced reinstatement of ethanol seeking.
RESUMO
While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.
RESUMO
O texto é um recorte de uma tese de doutorado que investiga, através de estudos de caso, a inserção curricular das TICs na formação de professores de três universidades recém-criadas na Região Sul do Brasil. Aqui, são descritas e analisadas as experiências mídia-educativas observadas no curso de Educação Física/Unipampa. A análise das propostas relacionadas às TICs foi baseada nas três dimensões da mídia-educação: instrumental, crítica e expressivo-produtiva. A metodologia qualitativa empregada envolveu análise documental, entrevistas e observações diretas para a produção de dados. A pesquisa mostrou um uso limitado das TICs no currículo estudado, com ênfase na abordagem disciplinar.
This article is part of PhD thesis that uses case studies to investigate the curricular inclusion of ICTs in teacher training at three recently created universities in southern Brazil. It describes and analyzes media-education experiences observed in Unipampas Physical Education. The analysis of the proposals related to ICTs was based on the three dimensions of media-education: instrumental, critical, and expressiveproductive. The qualitative methodology used involves document analysis, interviews and direct observation to produce data. The study found limited use of the ICTs in the curriculum studied, with an emphasis on the disciplinary approach.
Este texto es un recorte de una tesis de doctorado que investiga, a través de estudios de caso, la inserción curricular de las TICs en la formación de profesores de tres universidades recién creadas en la región Sur de Brasil. Son descritas y analizadas las experiencias de educación mediática observadas en el curso de Educación Física de la Unipampa. El análisis de las propuestas relacionadas con las TICs se basó en las tres dimensiones de educación mediática: instrumental, crítica y expresivo productiva. La metodología cualitativa utilizada incluyó análisis documental, entrevistas y observaciones directas para la producción de datos. La investigación reveló un uso limitado de las TICs en el currículo analizado, con énfasis en el abordaje disciplinario.